The main objective of this proposal is to study the hormonal regulation of growth and differentiated functions of normal epithelial cells. A nontumorigenic mouse Sertoli cell line inducible by follicle stimulating hormone and retinoic acid to produce plasminogen activator and other differentiated products in serum free medium will serve as a model system to investigate specific cell mechanisms of hormone action as well as interrelationships of different hormones. To carry out our objectives, we will use (1) homogeneous, synchronized cell populations, to determine the association of cell cycle events and hormone responsiveness (2) mutants, unresponsive to induction by hormones, in order to unravel the network of pathways leading to the production of a differentiated product (3) serum free medium, to study the effects of hormones, growth factors and vitamins in the absence of those and other unknown factors contributed by serum. Epithelial cells continue to be difficult to establish in culture, yet there is a need for such a culture model to study the mechanism of hormonal action on growth and differentiated functions. This need is strengthened by the fact that the majority of cancers are of epithelial derivation i.e. carcinomas. Such studies may suggest methods for increasing the effectiveness of hormonal therapy in human malignancy.